Maternal Thyroid Anomalies and Risk of Autism Spectrum Disorders

摘要

Background Thyroid hormones play pivotal roles in neurodevelopment. The fetus is dependent on maternal supply of thyroid hormones throughout gestation, suggesting that factors influencing maternal thyroid function may also relate to adverse neurodevelopmental effects in progeny. Impaired thyroid homeostasis has been linked with exposure to several environmental toxicants, yet consequences in the offspring remain unclear. We evaluated the risk of Autism Spectrum Disorders (ASD) in children born to mothers with thyroid anomalies, and the relation between gestational maternal thyroid levels and ASD risk. Methods The study included 436,188 singletons born in 1999-2013 in a large Israeli health fund. Data on ASD diagnoses, maternal thyroid conditions, drug dispensing and lab results were obtained through 2017. Mothers with thyroid conditions were identified through ICD9 codes with subsequent validation through review of drug dispensing data and lab results. ASD cases were identified through ICD9 codes and validated through review of medical records. Analyses were performed using generalized estimating equation (GEE) and general additive logistic regression models using penalized splines. Results Mothers who had ever experienced hypothyroidism were at a higher risk of having a child with ASD compared to women without thyroid conditions (aOR=1.28, 95% C.I:1.13-1.44). Stratified analysis based on time of first diagnosis indicated elevated risk estimates for diagnoses initially recorded both before and after the delivery date. Analysis of first-trimester TSH levels suggested a linear association with ASD risk at moderately elevated levels. Use of thyroid replacement medications during pregnancy did not mitigate the observed effects. Conclusions The results suggest that factors which influence thyroid metabolism could also play a role in the etiology of ASD. Environmental triggers known to influence thyroid function should be carefully evaluated for their neurodevelopmental effects.